<i>ALK‐</i>rearrangement in non‐small‐cell lung cancer (NSCLC)

Du, Xue; Shao, Yun; Qin, Haifeng; Tai, Yoshiaki; Gao, Hongjun

doi:10.1111/1759-7714.12613

Cited by 201 publications

(171 citation statements)

References 79 publications

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“…EML4-ALK is the most common gene fusion in NSCLC patients. Besides, a series of other ALK fusion partners have been discovered in NSCLC, including KIF5B, KLC1, and TPR, and most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor crizotinib[6].In our case, the DNA-based NGS suggested that LOC101927285-ALK rearrangement may form a LOC101927285-ALK fusion protein, which is probably inconsistent with the prediction of DNA breakpoint. But either way the positive Ventana staining and effectiveness of crizotinib indicates that this DNA rearrangement does lead to the activation of ALK fusion protein and drives the initiation of the tumor.…”

contrasting

confidence: 71%

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation

Zhao

Liu

et al. 2021

Cancer Res Treat

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A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

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contrasting

confidence: 71%

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation

Zhao

Liu

et al. 2021

Cancer Res Treat

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“…A genetic alteration of the anaplastic lymphoma kinase (ALK) gene is present in 3–5% of NSCLCs. Patients with this gene alteration are most often younger in age, female, and nonsmokers with adenocarcinoma [ 4 , 5 ]. The FDA approved the first ALK inhibitor, crizotinib, for ALK-positive locally advanced or metastatic NSCLC in 2011.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Waterhouse

Espirito

Chioda

et al. 2020

Drugs - Real World Outcomes

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Background Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Objective This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors. Patients and Methods This was a retrospective observational cohort study of adult patients with ALK-positive NSCLC treated with available first- and second-generation ALK inhibitors from 1 September 2011 to 31 December 2017. Duration of therapy (DOT) and overall survival (OS) were assessed with the Kaplan–Meier method. A multivariable linear regression analysis was performed to assess if DOT with a preceding ALK inhibitor was predictive of DOT for subsequent ALK inhibitor treatments. Results A total of 410 patients were analyzed: 57% received 1 ALK inhibitor; 35%, 2 ALK inhibitors; and 8%, 3–4 ALK inhibitors. Among those receiving > 1 ALK inhibitor ( n = 177), 60% received a crizotinib-led sequence and 39% an alectinib-led sequence. Nearly 60% of the overall population received chemotherapy prior to their first ALK inhibitor. Median OS for the study population was 28 months, 15 months in patients who received 1 ALK inhibitor, 42 months in patients who received 2 ALK inhibitors, and 56 months in patients who received 3–4 ALK inhibitors. Longer DOT of the first ALK inhibitor was associated with increased DOT of the second ( p < 0.0001), and longer DOT of the second ALK inhibitor was associated with increased DOT of the third ( p < 0.0001). Conclusions This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies.

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“…In 3–7% of cases, NSCLC is associated with various translocations in the ALK gene, leading to the formation of more than 19 chimeric proteins, including EML4, KIF5B, KLC1, and TPR. However, regardless of the genes involved in the translocation, all chimeric products retain the ALK kinase domain, which is responsible for constitutive oncogenic activation of the ALK signaling pathways (including Ras/Raf/MEK/ERK1/2, JAK/STAT, PI3K/Akt, PLC-γ signaling pathways) that regulate migration, proliferation, and cell survival [ 208 ]. Most chimeric ALKs are susceptible to the inhibitor crizotinib, which has been shown to be highly effective in the treatment of similar forms of NSCLC.…”

Section: Emt and Resistance To Antitumor Therapy: Role In The Formatimentioning

confidence: 99%

Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

et al. 2020

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About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

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ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

Cited by 201 publications

References 79 publications

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation

Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

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